Peripheral neuropathy

Revision as of 13:34, 11 January 2009 by Zorkun (talk | contribs) (→‎Causes)
Jump to navigation Jump to search
Peripheral neuropathy
ICD-10 G64, G90.0
ICD-9 356
DiseasesDB 9850
MeSH D010523

Template:Search infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [2] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.

Overview

Peripheral neuropathy describes damage to the peripheral nervous system, the vast communications network that transmits information from the brain and spinal cord (the central nervous system) to every other part of the body. Peripheral nerves also send sensory information back to the brain and spinal cord, such as a message that the feet are cold or a finger is burned. Damage to the peripheral nervous system interferes with these vital connections. Like static on a telephone line, peripheral neuropathy distorts and sometimes interrupts messages between the brain and the rest of the body. Because every peripheral nerve has a highly specialized function in a specific part of the body, a wide array of symptoms can occur when nerves are damaged. Some people may experience temporary numbness, tingling, and pricking sensations (paresthesia), sensitivity to touch, or muscle weakness. Others may suffer more extreme symptoms, including burning pain (especially at night), muscle wasting, paralysis, or organ or gland dysfunction. People may become unable to digest food easily, maintain safe levels of blood pressure, sweat normally, or experience normal sexual function. In the most extreme cases, breathing may become difficult or organ failure may occur.

Some forms of neuropathy involve damage to only one nerve and are called mononeuropathies. More often though, multiple nerves affecting all limbs are affected-called polyneuropathy. Occasionally, two or more isolated nerves in separate areas of the body are affected-called mononeuritis multiplex.

In acute neuropathies, such as Guillain-Barré syndrome, symptoms appear suddenly, progress rapidly, and resolve slowly as damaged nerves heal. In chronic forms, symptoms begin subtly and progress slowly. Some people may have periods of relief followed by relapse. Others may reach a plateau stage where symptoms stay the same for many months or years. Some chronic neuropathies worsen over time, but very few forms prove fatal unless complicated by other diseases. Occasionally the neuropathy is a symptom of another disorder.

In the most common forms of polyneuropathy, the nerve fibers (individual cells that make up the nerve) most distant from the brain and the spinal cord malfunction first. Pain and other symptoms often appear symmetrically, for example, in both feet followed by a gradual progression up both legs. Next, the fingers, hands, and arms may become affected, and symptoms can progress into the central part of the body. Many people with diabetic neuropathy experience this pattern of ascending nerve damage.

Types

More than 100 types of peripheral neuropathy have been identified, each with its own characteristic set of symptoms, pattern of development, and prognosis. Impaired function and symptoms depend on the type of nerves-motor, sensory, or autonomic-that are damaged. Motor nerves control movements of all muscles under conscious control, such as those used for walking, grasping things, or talking. Sensory nerves transmit information about sensory experiences, such as the feeling of a light touch or the pain resulting from a cut. Autonomic nerves regulate biological activities that people do not control consciously, such as breathing, digesting food, and heart and gland functions. Although some neuropathies may affect all three types of nerves, others primarily affect one or two types. Therefore, physicians may use terms such as predominantly motor neuropathy, predominantly sensory neuropathy, sensory-motor neuropathy, or autonomic neuropathy to describe a patient's condition.

Often the form of neuropathy is further broken down as to cause (see below), or other type, such as small fiber peripheral neuropathy, which is idiopathic.

There are other less common forms of neuropathy, for example Enteric Neuropathy

Peripheral neuropathy is not a disease in itself, but a symptom or a complication of other underlying conditions. Peripheral nerves, either singly or in groups, are damaged through lack of circulation, chemical imbalance, trauma, or other factors.[1]

Peripheral neuropathies may either be symmetrical and generalized or focal and multifocal, which is usually a good indicator of the cause of the peripheral nerve disease.

Generalized peripheral neuropathy

Generalized peripheral neuropathies are symmetrical, and usually due to various systematic illnesses and disease processes that affect the peripheral nervous system in its entirety. They are further subdivided into several categories:

Causes

Peripheral neuropathy may be either inherited or acquired. Causes of acquired peripheral neuropathy include physical injury (trauma) to a nerve, tumors, toxins, autoimmune responses, nutritional deficiencies, alcoholism, and vascular and metabolic disorders. Acquired peripheral neuropathies are grouped into three broad categories: those caused by systemic disease, those caused by trauma from external agents, and those caused by infections or autoimmune disorders affecting nerve tissue. One example of an acquired peripheral neuropathy is trigeminal neuralgia (also known as tic douloureux), in which damage to the trigeminal nerve (the large nerve of the head and face) causes episodic attacks of excruciating, lightning-like pain on one side of the face. In some cases, the cause is an earlier viral infection, pressure on the nerve from a tumor or swollen blood vessel, or, infrequently, multiple sclerosis. In many cases, however, a specific cause cannot be identified. Doctors usually refer to neuropathies with no known cause as idiopathic neuropathies.

Physical injury (trauma) is the most common cause of injury to a nerve. Injury or sudden trauma, such as from automobile accidents, falls, and sports-related activities, can cause nerves to be partially or completely severed, crushed, compressed, or stretched, sometimes so forcefully that they are partially or completely detached from the spinal cord. Less dramatic traumas also can cause serious nerve damage. Broken or dislocated bones can exert damaging pressure on neighboring nerves, and slipped disks between vertebrae can compress nerve fibers where they emerge from the spinal cord.

Systemic diseases: disorders that affect the entire body —often cause peripheral neuropathy. These disorders may include: Metabolic and endocrine disorders. Nerve tissues are highly vulnerable to damage from diseases that impair the body's ability to transform nutrients into energy, process waste products, or manufacture the substances that make up living tissue. Diabetes mellitus, characterized by chronically high blood glucose levels, is a leading cause of peripheral neuropathy in the United States. About 60 percent to 70 percent of people with diabetes have mild to severe forms of nervous system damage.

Kidney disorders can lead to abnormally high amounts of toxic substances in the blood that can severely damage nerve tissue. A majority of patients who require dialysis because of kidney failure develop polyneuropathy. Some liver diseases also lead to neuropathies as a result of chemical imbalances.

Hormonal imbalances can disturb normal metabolic processes and cause neuropathies. For example, an underproduction of thyroid hormones slows metabolism, leading to fluid retention and swollen tissues that can exert pressure on peripheral nerves. Overproduction of growth hormone can lead to acromegaly, a condition characterized by the abnormal enlargement of many parts of the skeleton, including the joints. Nerves running through these affected joints often become entrapped.

Vitamin deficiencies and alcoholism can cause widespread damage to nerve tissue. Vitamins E, B1, B6, B12, and niacin are essential to healthy nerve function. Thiamine deficiency, in particular, is common among people with alcoholism because they often also have poor dietary habits. Thiamine deficiency can cause a painful neuropathy of the extremities. Some researchers believe that excessive alcohol consumption may, in itself, contribute directly to nerve damage, a condition referred to as alcoholic neuropathy.

Vascular damage and blood diseases can decrease oxygen supply to the peripheral nerves and quickly lead to serious damage to or death of nerve tissues, much as a sudden lack of oxygen to the brain can cause a stroke. Diabetes frequently leads to blood vessel constriction. Various forms of vasculitis (blood vessel inflammation) frequently cause vessel walls to harden, thicken, and develop scar tissue, decreasing their diameter and impeding blood flow. This category of nerve damage, in which isolated nerves in different areas are damaged, is called mononeuropathy multiplex or multifocal mononeuropathy.

Connective tissue disorders and chronic inflammation can cause direct and indirect nerve damage. When the multiple layers of protective tissue surrounding nerves become inflamed, the inflammation can spread directly into nerve fibers. Chronic inflammation also leads to the progressive destruction of connective tissue, making nerve fibers more vulnerable to compression injuries and infections. Joints can become inflamed and swollen and entrap nerves, causing pain.

Cancers and benign tumors can infiltrate or exert damaging pressure on nerve fibers. Tumors also can arise directly from nerve tissue cells. Widespread polyneuropathy is often associated with the neurofibromatoses, genetic diseases in which multiple benign tumors grow on nerve tissue. Neuromas, benign masses of overgrown nerve tissue that can develop after any penetrating injury that severs nerve fibers, generate very intense pain signals and sometimes engulf neighboring nerves, leading to further damage and even greater pain. Neuroma formation can be one element of a more widespread neuropathic pain condition called complex regional pain syndrome or reflex sympathetic dystrophy syndrome, which can be caused by traumatic injuries or surgical trauma. Paraneoplastic syndromes, a group of rare degenerative disorders that are triggered by a person's immune system response to a cancerous tumor, also can indirectly cause widespread nerve damage.

Repetitive stress frequently leads to entrapment neuropathies, a special category of compression injury. Cumulative damage can result from repetitive, forceful, awkward activities that require flexing of any group of joints for prolonged periods. The resulting irritation may cause ligaments, tendons, and muscles to become inflamed and swollen, constricting the narrow passageways through which some nerves pass. These injuries become more frequent during pregnancy, probably because weight gain and fluid retention also constrict nerve passageways.

Toxins can also cause peripheral nerve damage. People who are exposed to heavy metals (arsenic, lead, mercury, thallium), industrial drugs, or environmental toxins frequently develop neuropathy. Certain anticancer drugs, anticonvulsants, antiviral agents, and antibiotics have side effects that can include peripheral nerve damage, thus limiting their long-term use.

Infections and autoimmune disorders can cause peripheral neuropathy. Viruses and bacteria that can attack nerve tissues include herpes varicella-zoster (shingles), Epstein-Barr virus, cytomegalovirus, and herpes simplex-members of the large family of human herpes viruses. These viruses severely damage sensory nerves, causing attacks of sharp, lightning-like pain. Postherpetic neuralgia often occurs after an attack of shingles and can be particularly painful.

The human immunodeficiency virus (HIV), which causes AIDS, also causes extensive damage to the central and peripheral nervous systems. The virus can cause several different forms of neuropathy, each strongly associated with a specific stage of active immunodeficiency disease. A rapidly progressive, painful polyneuropathy affecting the feet and hands is often the first clinically apparent sign of HIV infection.

Lyme disease, diphtheria, and leprosy are bacterial diseases characterized by extensive peripheral nerve damage. Diphtheria and leprosy are now rare in the United States, but Lyme disease is on the rise. It can cause a wide range of neuropathic disorders, including a rapidly developing, painful polyneuropathy, often within a few weeks after initial infection by a tick bite.

Viral and bacterial infections can also cause indirect nerve damage by provoking conditions referred to as autoimmune disorders, in which specialized cells and antibodies of the immune system attack the body's own tissues. These attacks typically cause destruction of the nerve's myelin sheath or axon (the long fiber that extends out from the main nerve cell body).

Some neuropathies are caused by inflammation resulting from immune system activities rather than from direct damage by infectious organisms. Inflammatory neuropathies can develop quickly or slowly, and chronic forms can exhibit a pattern of alternating remission and relapse. Acute inflammatory demyelinating neuropathy, better known as Guillain-Barré syndrome, can damage motor, sensory, and autonomic nerve fibers. Most people recover from this syndrome although severe cases can be life threatening. Chronic inflammatory demyelinating polyneuropathy (CIDP), generally less dangerous, usually damages sensory and motor nerves, leaving autonomic nerves intact. Multifocal motor neuropathy is a form of inflammatory neuropathy that affects motor nerves exclusively; it may be chronic or acute.

Inherited forms of peripheral neuropathy are caused by inborn mistakes in the genetic code or by new genetic mutations. Some genetic errors lead to mild neuropathies with symptoms that begin in early adulthood and result in little, if any, significant impairment. More severe hereditary neuropathies often appear in infancy or childhood.

The most common inherited neuropathies are a group of disorders collectively referred to as Charcot-Marie-Tooth disease. These neuropathies result from flaws in genes responsible for manufacturing neurons or the myelin sheath. Hallmarks of typical Charcot-Marie-Tooth disease include extreme weakening and wasting of muscles in the lower legs and feet, gait abnormalities, loss of tendon reflexes, and numbness in the lower limbs.

As a summary; aside from diabetes (see Diabetic neuropathy), the common causes of neuropathy are herpes zoster infection, HIV-AIDS, toxins, alcoholism, chronic trauma (such as repetitive motion disorders) or acute trauma (including surgery), various neurotoxins and autoimmune conditions such as celiac disease, which can account for approximately 16% of small fiber neuropathy cases.[2] Neuropathic pain is common in cancer as a direct result of the cancer on peripheral nerves (e.g., compression by a tumor), as a side effect of many chemotherapy drugs, and as a result of electrical injury. In many cases the neuropathy is "idiopathic," meaning no cause is found. A form of spinal nerve entrapment called Posterior Rami Syndrome can led to neuropathic pain.

The List of Causes of Peripheral neuropathy

  • Genetic diseases:
  • Metabolic / Endocrine:
  • Toxic causes:
  • Inflammatory diseases:
  • Vitamin deficiency states:

Complete Differential Diagnosis for Peripheral Neuropathy

Signs and symptoms

Symptoms are related to the type of affected nerve and may be seen over a period of days, weeks, or years. Muscle weakness is the most common symptom of motor nerve damage. Other symptoms may include painful cramps and fasciculations (uncontrolled muscle twitching visible under the skin), muscle loss, bone degeneration, and changes in the skin, hair, and nails. These more general degenerative changes also can result from sensory or autonomic nerve fiber loss.

Sensory nerve damage causes a more complex range of symptoms because sensory nerves have a wider, more highly specialized range of functions. Larger sensory fibers enclosed in myelin (a fatty protein that coats and insulates many nerves) register vibration, light touch, and position sense. Damage to large sensory fibers lessens the ability to feel vibrations and touch, resulting in a general sense of numbness, especially in the hands and feet. People may feel as if they are wearing gloves and stockings even when they are not. Many patients cannot recognize by touch alone the shapes of small objects or distinguish between different shapes. This damage to sensory fibers may contribute to the loss of reflexes (as can motor nerve damage). Loss of position sense often makes people unable to coordinate complex movements like walking or fastening buttons, or to maintain their balance when their eyes are shut.

Neuropathic pain is difficult to control and can seriously affect emotional well-being and overall quality of life. Neuropathic pain is often worse at night, seriously disrupting sleep and adding to the emotional burden of sensory nerve damage. Neuropathic pain is usually perceived as a steady burning and/or "pins and needles" and/or "electric shock" sensations and/or tickling. The difference is due to the fact that "ordinary" pain stimulates only pain nerves, while a neuropathy often results in the firing of both pain and non-pain (touch, warm, cool) sensory nerves in the same area, producing signals that the spinal cord and brain do not normally expect to receive.

Smaller sensory fibers without myelin sheaths transmit pain and temperature sensations. Damage to these fibers can interfere with the ability to feel pain or changes in temperature. People may fail to sense that they have been injured from a cut or that a wound is becoming infected. Others may not detect pains that warn of impending heart attack or other acute conditions. (Loss of pain sensation is a particularly serious problem for people with diabetes, contributing to the high rate of lower limb amputations among this population.) Pain receptors in the skin can also become oversensitized, so that people may feel severe pain (allodynia) from stimuli that are normally painless (for example, some may experience pain from bed sheets draped lightly over the body).

Symptoms of autonomic nerve damage are diverse and depend upon which organs or glands are affected. Autonomic nerve dysfunction can become life threatening and may require emergency medical care in cases when breathing becomes impaired or when the heart begins beating irregularly. Common symptoms of autonomic nerve damage include an inability to sweat normally, which may lead to heat intolerance; a loss of bladder control, which may cause infection or incontinence; and an inability to control muscles that expand or contract blood vessels to maintain safe blood pressure levels. A loss of control over blood pressure can cause dizziness, lightheadedness, or even fainting when a person moves suddenly from a seated to a standing position (a condition known as postural or orthostatic hypotension).

Gastrointestinal symptoms frequently accompany autonomic neuropathy. Nerves controlling intestinal muscle contractions often malfunction, leading to diarrhea, constipation, or incontinence. Many people also have problems eating or swallowing if certain autonomic nerves are affected.

Numbness is an abnormal sensation called dysesthesias and allodynias that occur either spontaneously or in reaction to external stimuli, and a characteristic form of pain, called neuropathic pain or neuralgia, that is qualitatively different from the ordinary nociceptive pain one might experience from stubbing a toe or hitting a finger with a hammer.

Those with diseases or dysfunctions of their peripheral nerves can present with problems in any of the normal peripheral nerve functions.

In terms of sensory function, there are commonly loss of function (negative) symptoms, which include numbness, tremor, and gait imbalance.

Gain of function (positive) symptoms include tingling, pain, itching, crawling, and pins and needles. Pain can become intense enough to require use of opiate drugs (i.e., morphine, oxycontin).

Skin can become so hypersensitive that patients are prohibited from having anything touch certain parts of their body, especially the feet. People with this degree of sensitivity cannot have a bed sheet touch their feet or wear socks or shoes, and eventually become housebound.

Motor symptoms include loss of function (negative) symptoms of weakness, tiredness, heaviness, and gait abnormalities; and gain of function (positive) symptoms of cramps, tremor, and fasciculations.

There is also pain in the muscles (myalgia), cramps, etc., and there may also be autonomic dysfunction.

During physical examination, those with generalized peripheral neuropathies most commonly have distal sensory or motor and sensory loss, though those with a pathology (problem) of the peripheral nerves may be perfectly normal; may show proximal weakness, as in some inflammatory neuropathies like Guillain-Barré syndrome); or may show focal sensory disturbance or weakness, such as in mononeuropathies, radiculopathies and plexopathies.

Common disorders of the peripheral nerves include focal entrapment neuropathies (e.g., carpal tunnel syndrome), generalized peripheral neuropathies (e.g., diabetic neuropathy), plexopathies (e.g., brachial neuritis) and radiculopathies (e.g., of cranial nerve VII; Facial nerve).

Treatment of neuropathic pain

Neuropathic pain can be very difficult to treat. Sometimes strong opioid analgesics may provide only partial relief. Opioid analgesics are to be considered only as a tertiary treatment. Several classes of medications not normally thought of as analgesics are often effective, alone or in combination with opioids and other treatments. These include tricyclic antidepressants such as amitriptyline (Elavil®), anticonvulsants such as gabapentin (Neurontin®) and pregabalin (Lyrica®).

In animal models of neuropathic pain it has been found that compounds which only block serotonin reuptake do not improve neuropathic pain.[3][4][5][6][7][8][9][10] Similarly, compounds that only block norepinephrine reuptake also do not improve neuropathic pain. Compounds such as duloxetine, venlafaxine, and milnacipran that block both serotonin reuptake and norepinephrine reuptake do improve neuropathic pain. Antidepressants usually reduce neuropathic pain more quickly and with smaller doses than they relieve depression. Antidepressants therefore seem to work differently on neuropathic pain than on depression, perhaps by activating descending norepinephrinergic and serotonergic pathways in the spinal cord that block pain signals from ascending to the brain.

Many of the pharmacologic treatments for chronic neuropathic pain decrease the sensitivity of nociceptive receptors, or desensitize C fibers such that they transmit fewer signals. The newer anticonvulsants gabapentin and pregabalin appear to work by blocking calcium channels in damaged peripheral neurons. Tricyclic antidepressants may also work on sodium channels in peripheral nerves. The anticonvulsants carbamazepine (Tegretol®) and oxcarbazepine (Trileptal®), especially effective on trigeminal neuralgia, are thought to work principally on sodium channels.

In general, the antidepressants seem to be most effective on continuous burning pain, while the anticonvulsants seem to work best on sudden, lancinating, "shock-like" pains that appear to involve large numbers of peripheral nerves improperly firing together.

In some forms of neuropathy, especially post-herpes neuralgia, the topical application of local anesthetics such as lidocaine can provide relief. A transdermal patch containing 5% lidocaine is available. Ketamine in a transdermal gel is also frequently effective when the neuropathy is localized. Neurontin 100mg/g PLO gel is also effective for treating peripheral neuropathy, including Carpal Tunnel Syndrome. Capsaicin cream can be beneficial in several neurogenic pain disorders, which causes release of the pain neurotransmitter Substance P, and eventually reduces the availability of Substance P.

Transcutaneous electrical nerve stimulation (TENS) is worth a trial in chronic neurogenic pain. Some pain management specialists will try acupuncture, with variable results. TENS, with certain electrical waveforms, appears to have an acupuncture-like function.

In some neuropathic pain syndromes, "crosstalk" occurs between descending sympathetic nerves and ascending sensory nerves. Increases in sympathetic nervous system activity result in an increase of pain; this is known as sympathetically-mediated pain. Reducing the sympathetic nerve activity in the painful region with local nerve blocks or systemic medications such as the alpha-blocker clonidine may provide relief. Other drugs, known for their ability to desensitize cardiac tissue, include beta-blockers such as propanolol and calcium channel blockers such as verapamil.

The NMDA receptor seems to play a major role in neuropathic pain and in the development of opioid tolerance, and many experiments in both animals and humans have established that NMDA antagonists such as ketamine and dextromethorphan can alleviate neuropathic pain and reverse opioid tolerance. Unfortunately, only a few NMDA antagonists are clinically available and their use is usually associated with unacceptable side effects.

Several opioids, particularly methadone, have NMDA antagonist activity in addition to their μ-opioid agonist properties that seems to make them effective against neuropathic pain, although this is still the subject of intensive research and clinical study. Methadone has this property because it is a racemic mixture; one stereo-isomer is a μ-opioid agonist; the other is a NMDA antagonist.

A recent study showed smoking marijuana is beneficial in treating HIV-associated periphial neuropathy.[11]

In addition to pharmacological treatment there are several other modalities that help some cases. While lacking double blind trials, these have shown to reduce pain and improve patient quality of life particularly for chronic neuropathic pain: Interferential Stimulation; Acupuncture; Meditation; Cognitive Therapy; and prescribed exercise.

In more recent years, infrared photo therapy has been used to treat neuropathic symptoms. Photo therapy devices emit near infrared light typically at a wavelength of 890nm. This wavelength is believed to stimulate the release of nitric oxide, an endothelium-derived relaxing factor into the bloodstream, thus vasodilating the capilaries and venuoles in the microcirculatory system. This increase in circulation has been shown effective in various clinical studies, to decrease pain and improve sensation in diabetic and non-diabetic patients. Note that the U.S. FDA has not approved any infrared photo therapy devices to treat neuropathy.[12]

Alternative medicine treatments

There are 2 dietary supplements that have clinical evidence showing them to be effective treatments of diabetic neuropathy; alpha lipoic acid and benfotiamine. In several studies using a variety of dosages and routes of administration, alpha lipoic acid was found to reduce the various symptoms of peripheral diabetic neuropathy. A recent review of the published data determined “ALA should be considered as a treatment option for patients with peripheral diabetic neuropathy.” Also a recent study using orally administered alpha lipoic acid found that 600 mg once a day caused a marked reduction in the symptoms of diabetic neuropathy including stabbing pain, burning pain, paresthesia, and asleep numbness of the feet. Benfotiamine is a lipid soluble form of thiamine that has several placebo controlled double blind trials proving efficacy in treating neuropathy and various other diabetic comorbidities. 400 mg a day was the most commonly studied dose.

See also

References

  1. Ruth Werner, LMP, NCTMB A Massage Therapist's Guide to Pathology; Third Edition Copyright 2005
  2. "Up to 16% of Patients with Small Fiber Neuropathy May Have Celiac Disease". Celiac.com. Retrieved 2007-26-06. Check date values in: |accessdate= (help)
  3. Bennett G, Xie Y (1988). "A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man". Pain. 33 (1): 87–107. PMID 2837713.
  4. Seltzer Z, Dubner R, Shir Y (1990). "A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury". Pain. 43 (2): 205–18. PMID 1982347.
  5. Kim S, Chung J (1992). "An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat". Pain. 50 (3): 355–63. PMID 1333581.
  6. Malmberg A, Basbaum A (1998). "Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates". Pain. 76 (1–2): 215–22. PMID 9696476.
  7. Sung B, Na H, Kim Y, Yoon Y, Han H, Nahm S, Hong S (1998). "Supraspinal involvement in the production of mechanical allodynia by spinal nerve injury in rats". Neurosci. Lett. 246 (2): 117–9. PMID 9627194.
  8. Lee B, Won R, Baik E, Lee S, Moon C (2000). "An animal model of neuropathic pain employing injury to the sciatic nerve branches". Neuroreport. 11 (4): 657–61. PMID 10757496.
  9. Decosterd I, Woolf C (2000). "Spared nerve injury: an animal model of persistent peripheral neuropathic pain". Pain. 87 (2): 149–58. PMID 10924808.
  10. Vadakkan K, Jia Y, Zhuo M (2005). "A behavioral model of neuropathic pain induced by ligation of the common peroneal nerve in mice". The journal of pain : official journal of the American Pain Society. 6 (11): 747–56. PMID 16275599.
  11. Abrams D, Jay C, Shade S, Vizoso H, Reda H, Press S, Kelly M, Rowbotham M, Petersen K (2007). "Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial". Neurology. 68 (7): 515–21. PMID 17296917.
  12. http://www.healthlight.stirsite.com/page/page/2909659.htm

Additional Resources

Neuropathy related organizations

External links

Acknowledgements

The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.

Template:PNS diseases of the nervous system Template:SIB

de:Neuropathie it:Neuropatia nl:Neuropathie it:Neuropatia periferica


Template:WikiDoc Sources